Heart failure is a major cause of death in the US, and the problem is growing as our population ages. Each year 500,000 new cases are diagnosed resulting in $10 billion in healthcare costs. Earlier detection of heart failure can improve patient care and help stem increasing healthcare costs. Improvement in nuclear medicine imaging methods to better detect heart disease depends on three technologies: radiopharmaceuticals that are specific for perfusion and metabolic status, instrumentation improvements for better resolution and temporal data acquisition, and data analysis innovations that remove artifacts of motion, attenuation, scatter and misregistration. This application proposes small improvements in current instrumentation and major improvements in reconstruction algorithms. Because most cardiac SPECT procedures use a large field-of-view rotating gamma camera, converging collimation can be used to improve the geometric efficiency and resolution of SPECT images for organs the size of the heart. The goal is to improve diagnosis of heart failure by improving technology of quantitative cardiac SPECT with converging collimation and merging that technology with x-ray CT. Algorithms and methodology for cone-beam tomography using SPECT-CT are required for development of this technology. Merging of x-ray CT with SPECT will help develop better models for emission perfusion and biomechanical deformation imaging and will aid in correcting for artifacts caused by inadequate modeling of the physics of the image detection process. New hybrid SPECT-CT technology holds the potential to improve both short- and long-term stratification of care for patients with cardiac disease. Mechanical models will be used to simulate gated cardiac SPECT data for human and numerical observer experiments, to directly measure the mechanical properties of the heart in patients, and to improve gated cardiac SPECT image quality. The new technology will improve spatial and contrast resolution of cardiac images, quantification of radiopharmaceutical uptake, visualization of wall motion, and potentially sensitivity and specificity in diagnosing heart failure using contemporary commercial SPECT-CT instruments installed in clinics throughout the world. Outcomes will include: (1) new algorithms for reconstruction of 3D images of the heart without artifacts from projections obtained using converging collimators, (2) verification that 3D mechanical modeling of the beating heart improves quality of gated cardiac SPECT images, and (3) an assessment of the capabilities of SPECT-CT to provide the same quality of information as can be obtained from the more expensive and less convenient PET technology. The relevance to the NIH mission and public health is improved diagnosis of heart failure that can improve patient care by incorporating x-ray CT data and new algorithms for cardiac SPECT. [unreadable] [unreadable] [unreadable]